Several patterns of hippocampal cell loss are observed in the clinical population with focal epilepsy of temporal lobe origin. It is generally agreed that seizures, with associated ischemic/hypoxic distress, predate this hippocampal damage. Once produced, however, there has been little work to determine if this cell damage contributes to the progression of epilepsy. The present proposal examines the acute and chronic physiologic, morphologic and neurochemical consequences of these clinically relevant lesions produced in both adult and developing rats. Lesions of hippocampal subfield CA3, or the "end blade", will be produced by intraventricular kainic acid. Lesions of hippocampal subfield CA1, or "Sommer's sector", will be produced by transient forebrain ischemia. The development of epileptogenesis in remaining neurons will be determined by in vivo subcortical recording or in vitro recording in the hippocampal slice preparation. Each treatment will be analyzed further to determine contributing neuroplastic rearrangements in hippocampus which may promote, or prevent, epileptogenesis. The integrity of hippocampal inhibitory neurons and receptors for GABA, will be determined by GAD immunocytochemistry and quantitative in vitro autoradiography. Alterations in hippocampal excitatory function will be determined by similar immunocytochemical and autoradiographic methods examining glutamate and its several post-synaptic receptor subtypes. Specific hypotheses include: 1) lesions of CA3 will produce epileptogenesis in adults, as has already been demonstrated; they will not be epiletogenic when produced in neonates, primarily because of a different pattern of reactive sprouting in hippocampus; 2) loss of CA1 will be epileptogenic when produced in both young and adult animals; young animals may be more severely affected primarily due to extensive recurrent excitatory collateral sprouting in remaining CA3 neurons; 3) epileptogenic treatments will be accompanied by abnormal morphologic and functional interactions between inhibitory and excitatory neurons in the hippocampus and by specific changes in transmitter immunoreactivity and receptors. The work proposed will provide a needed body of data on the consequences of lesions frequently observed in human hippocampus. It will further identify the age dependence of the lesions sequelae. Such information could provide a foundation for assessing the need for, and designing, interventive treatments in the clinical population suffering from lesion producing trauma and/or seizures.